Drug information of Pholcodine

Pholcodine

Drug group:

Pholcodine formula is 3-o-morpholinoethylmorphine and it is classified as an antitussive which is defined as an opioid cough suppressant. It belongs to the opioid family of compounds and it is widely used. Pholcodine activity is the suppression of unproductive cough and it also has a mild sedative effect with little or no analgesic effects. Pholcodine is not prescribed in the United States where it is classed as a Schedule I drug. It is categorized as Class B drug in the UK and officially taken out of the shelves in 2008. Pholcodine is not approved in Canada
Pholcodine Linctus works well on an irritating, dry and tickly cough, by providing soothing relief. As a cough suppressant, it stops the urge to cough and also relieves chest irritation.

This medication works by clearing mucus, dust particles and bacteria from both throat and lungs, the presence of which irritate the airways and make breathing more difficult. However, there are times when there is no mucus present, and no phlegm released, resulting in a purposeless cough, accompanied by pain and frustration. In these cases, pholcodine works by reducing the nerve signals which tell the coughing centre in the brain to try to clear what is not actually there.

Pholcodine should not be used at the same time as taking any other medicines for coughs or colds, as they could contain the same active ingredients and lead to you exceeding the daily recommendation. Also, cough expectorants can produce an opposite reaction and so advice should always be taken from your doctor or a pharmacist..

Mechanism of effect

The mechanism of action of pholcodine is directly performed in the medulla oblongata. In this site, it exerts analgesic properties on the peripheric reflexogenic receptors. This site is commonly known as the "cough center.

Pharmacodynamic

The therapeutic doses of pholcodine have been shown not to cause depression of respiration, CNS excitation or other side effects associated with narcotics. It is thought that the impact of pholcodine is selective on the cough center without affecting the respiratory center. Pholcodine is not euphorigenic, and thus, psychological dependence is unlikely. Clinical trials have not shown any evidence of addiction after prolonged administration of pholcodine.6 It is well reported that pholcodine presents a more considerable respiratory depression effect than codeine and it causes hypotension in the same degree than codeine. Some other noted impacts of pholcodine in preclinical trials are: 1) the induction of histamine release, 2) anti-histaminic effect, 3) anti-acetylcholinic action, 4) anti-convulsant action and 5) mild tranquilizing action

Pharmacokinetics

    After oral administration of 60 mg of pholcodine, the Tmax and Cmax are reported to be 1.3 hours and 26.3 ng/ml. In the same administration, the AUC in plasma and saliva are reported to be 1.67 and 6.61 mg h/l respectively. The absorption of pholcodine is reported to represent approximately 88% of the administered dose.1
Volume of distribution
    The reported volume of distribution depends on the pharmacokinetic model and it can be of 265L based on a one-compartment model to 3207L in a two-compartment model.4
Protein binding
    The protein binding of pholcodine is of approximately of 21-23% and it tends to have a slight variation depending if the administration is chronic.1
Metabolism
    The metabolism of pholcodine seems to be very slow4 and due to the elimination profile, it is thought that most of the administered dose undergoes metabolism. There is some evidence in preclinical trials that indicate that morphine is a minor metabolite of pholcodine and that it accounts for 1% of the administered dose
Route of elimination

After oral administration of pholcodine, the serum concentration peaks and declines in a monoexponential manner. The percent of the dose excreted unchanged is of approximately 25-30%. Part of the administered dose is composed by metabolites that can be recovered in urine. From the administered dose, the fecal excretion corresponds to the 5% of the administered dose as unchanged pholcodine.1

Half-life

After oral administration of 60 mg of pholcodine, the half-life in plasma, saliva and urine are 45, 55 and 45 hours respectively.1

Clearance

After oral administration of 60 mg of pholcodine, the clearance rate was reported to be 126 ml/min.1

Drug indications

Adults: Cough suppressant for relief of acute non-productive cough associated with upper respiratory tract infection

Children of 6-12 years of age: Cough suppressant for relief of acute non-productive cough associated with upper respiratory tract infection.

Dosage

Adults: 10 ml up to six times in any 24 hours.
Dosage should be reduced in elderly or debilitated patients.
Children 6-12 years: 5 ml up to four times in any 24 hours.
Pholcodine is contraindicated in children under the age of 6 years (see section 4.3)
Children of 6-12 years of age: not to be used for more than 5 days without the advice of a doctor. Parents or carers should seek medical attention if the child's condition deteriorates during treatment
Do not exceed the stated dose

Drug contraindications

Pholcodine should not be given to subjects in or at risk of developing respiratory failure as the sedative properties of pholcodine may exacerbate the condition.

Patients with chronic bronchitis, COPD, bronchiolitis or bronchiectasis due to sputum retention

Patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping such treatment (see also section 4.5).

Patients with hypersensitivity or idiosyncratic response to pholcodine or to any of the excipients.

 

Patients with liver disease since pholcodine is metabolised in the liver and the drug may accumulate.

Not to be used in children under the age of 6 years.

Side effects

The following side effects may be associated with the use of Pholcodine:
Occasional drowsiness, dizziness, excitation, confusion, sputum retention, vomiting, gastrointestinal disturbances (nausea and constipation) and skin reactions including rash.
Immune system disorders have been noted including hypersensitivity reactions and anaphylaxis.
Skin and subcutaneous tissue disorders
Unknown: Acute generalized exanthematous pustulosis

Interactions

Ramipril , Rotigotine , Tolcapone

The reduction in blood pressure caused by antihypertensives may accentuate the hypotensive effects of pholcodine. Diuretics may have a similar effect. The sedative effects of central nervous system depressants may be increased by alcohol, barbiturates, hypnotics, narcotic analgesics, sedatives and tranquillisers (phenothiazines and tricyclic antidepressants).

Hypertensive crisis may be caused by concurrent use of pholcodine with monoamine – oxidase inhibitors therefore not to be used in patients taking MAOIs or within 14 days of stopping treatment.

Interaction with neuromuscular blocking agents (anaphylaxis) has been reported.

Alerts

1. Should be used with caution by patients with liver or renal impairment

2. Ask a doctor before use if you suffer from a chronic or persistent cough, if you have asthma, suffering from acute asthma attack or where cough is accompanied by excessive secretions

3. Do not take with any other cough and cold medicine

4. Use of Pholcodine with alcohol or other CNS depressants may increase the effects on the CNS and cause toxicity in relatively smaller doses

5. Children and elderly patients should be supervised while taking this medication.

6. Caution is needed in patients with a history of drug abuse. Pholcodine is an opioid and addiction is observed with opioids as a class.

7. Patients with rare hereditary problems of fructose intolerance should not take this medicine.

8. Sunset yellow (E110) may cause allergic reactions.

9. Severe cutaneous adverse reactions (SCARs) including acute generalized exanthematous pustulosis (AGEP), which can be life-threatening or fatal, have been reported in patients treated with pholcodine, most likely in the first week. Patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, this medicine should be withdrawn immediately.

Pregnancy level

Risk – benefit must be considered before using pholcodine during pregnancy or lactation. Opioid analgesics cross the placenta. Regular use during pregnancy may cause physical dependency and respiratory difficulties in the foetus, leading to withdrawal symptoms in the neonate, particularly in the premature neonate. There is a risk of gastric stasis in the mother during labour which may lead to inhalation pneumonia. Teratogenic effects in humans have not been documented but controlled studies have not been done, nor have studies in animals been documented for pholcodine. Although it is known that some opioid analgesics are excreted in breast milk, information on the excretion of pholcodine in breast milk is lacking.


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